This project was initiated to study the pineal as a model to learn how nerves interact with responsive cells. There is a prominent circadian rhythm in the post junctional sensitivity of the pineal to stimulation by Beta-adrenergic agonists. This variation is regulated at multiple sites, each of which is involved in the generation of the pineal's response to stimulation via cyclic AMP and N-acetyltransferase. Both cyclic nucleotides are released from the pineal: cyclic AMP is released by parenchymal cells whereas cyclic GMP is released from the noradrenergic nerve endings in the gland. The release of cyclic GMP was also demonstrated from the peptidergic nerve endings in the posterior pituitary. BIBLIOGRAPHIC REFERENCES: Zatz, M., Kebabian, J.W., Romero, J.A., Lefkowitz, R.J., and Axelrod, J.: Pineal Beta-adrenergic Receptor: Correlation of Binding of 3H-(1)-alprenolol with Stimulation of Adenylate Cyclase. J. Pharmacol. Exp. Ther. 196: 714-722, 1976. Zatz, M., and O'Dea, R.F.: Efflux of Cyclic Nucleotides from Rat Pineal: Release of Cyclic GMP from Sympathetic Nerve Endings. Science 197: 174-175, 1977.